Gleason 6 prostate cancer: surgery or active surveillance?

What does Gleason 6, or grade group 1, mean?

Gleason 3+3=6 is the lowest grade of prostate cancer that is reported on a biopsy today, and it corresponds to ISUP grade group 1, the first of 5 groups. The pathologist grades the most extensive growth pattern in the sample and the second most common one, and adds the two. Patterns 1 and 2 are no longer used, so 3+3 is where the scale starts.

The EAU guideline is unusually direct about this grade. It states that grade group 1 cancer found in a removed prostate does not itself behave in a clinically malignant way, and that in large studies of prostates containing only grade group 1 cancer, spread to the seminal vesicles or lymph nodes was not seen at all.

Two cautions belong beside that statement:

• A biopsy is a sample. It examines a small part of the gland, so a higher-grade area can be missed. This is covered below.
• Grade can change. According to the guideline, grade group 1 may progress to higher grades at a rate of approximately 1% per year.

Gleason 6 and "low risk" are also not the same thing. In the EAU risk groups, low risk means grade group 1 together with a PSA below 10 ng/mL and a tumour that is stage cT1 to cT2 on examination. With a PSA of 10 to 20 ng/mL, the same Gleason 6 cancer is classed as favourable intermediate risk.

Why do guidelines put active surveillance first?

Because very few of these cancers threaten life, while every curative treatment has side effects. The 2026 EAU guideline states that for men with low-risk prostate cancer and an adequate life expectancy, active surveillance is the first management option. Its recommendation to offer active surveillance as the standard of care to all suitable patients carries a strong rating, the higher of the guideline's two grades.

The same guideline notes that active treatment mostly benefits men with intermediate-risk or high-risk cancer and the longest expected survival. A surgeon who tells a man with Gleason 6 that he may not need an operation is repeating what the evidence says.

Active surveillance is not the same as doing nothing, and it is not watchful waiting. The intention stays curative: the cancer is checked on a schedule, and treatment is given if it shows signs of becoming dangerous. Watchful waiting is a different approach for men whose life expectancy is limited, in which treatment is given only for symptoms.

One exclusion is firm. The guideline gives a strong recommendation that men whose biopsy shows cribriform or intraductal growth should not be managed with active surveillance.

What do the long-term trials show?

Over 15 years, death from prostate cancer was uncommon whether men were monitored, operated on or given radiotherapy, and the differences between the groups were not significant. The price of monitoring was a higher rate of metastases.

ProtecT is the main randomised trial. In the United Kingdom, 1,643 men with localised prostate cancer found by PSA testing were assigned to active monitoring (545 men), prostatectomy (553) or radiotherapy (545) and followed for a median of 15 years. Death from prostate cancer occurred in 17 men (3.1%) in the monitoring group, 12 (2.2%) in the surgery group and 16 (2.9%) in the radiotherapy group. Metastases developed in 51 (9.4%), 26 (4.7%) and 27 (5.0%).

The older PIVOT trial in the United States assigned 731 men to prostatectomy or observation and followed them for up to 19.5 years. Among men with low-risk disease, all-cause mortality differed by 0.7 percentage points between the groups, with a confidence interval that included no difference.

Limits: more than one third of the men in ProtecT had intermediate-risk or high-risk disease at diagnosis, so its figures are not those of a pure Gleason 6 group. Recruitment ran from 1999 to 2009, and the guideline points out that the trial's active monitoring was a less stringent strategy than present-day active surveillance, relying on PSA without scheduled repeat biopsies. PIVOT compared surgery with observation, not with active surveillance. The surveillance cohorts are not randomised, two come from single centres, and median follow-up was 5.0 years in one and 6.4 years in the other.

What does active surveillance involve in practice?

Regular PSA tests, an examination, MRI and repeat biopsies, continued for as long as curative treatment would still make sense. The EAU guideline asks for a strict protocol and gives a strong recommendation for its core elements. Programmes differ in the details; the table shows what the guideline describes.

The guideline notes that there is no consensus on how often biopsies should be repeated. Your own schedule is set by your urologist.

Three points from the guideline are worth knowing before you start:

• A rising PSA is a signal, not a verdict. A PSA doubling time of under 3 years should lead to an MRI and a repeat biopsy, not directly to treatment.
• The biopsy decides. The guideline advises basing a change of treatment on biopsy findings, not on MRI, PSA or examination alone (weak recommendation).
• Surveillance has an end point. It continues until life expectancy falls below 10 years, after which monitoring can be simplified to watchful waiting.

How many men on surveillance eventually have treatment, and why?

A substantial share, most often because a later biopsy shows a higher grade. The EAU guideline puts it at more than one third of men reclassified during follow-up. Moving to treatment is part of the plan when the cancer changes, not a sign that surveillance failed.

• Toronto (Klotz and colleagues). In a prospective single-centre cohort of 993 men with favourable-risk or intermediate-risk cancer, 75.7% were still untreated and on surveillance at 5 years, 63.5% at 10 years and 55.0% at 15 years. In all, 1.5% died of prostate cancer and 2.8% developed metastatic disease.
• Johns Hopkins (Tosoian and colleagues). Among 1,818 men with grade group 1 cancer, biopsy grade reclassification occurred in 21% by 5 years, 30% by 10 years and 32% by 15 years, and 48% had switched to treatment by 10 years. The cumulative incidence of metastasis or death from prostate cancer was 0.1% at both 10 and 15 years. The authors note that their selection and monitoring are stricter than in many other programmes.
• GAP3 (21 centres in 12 countries). Among 10,296 men, 43.6% left surveillance within 5 years. Signs of progression were seen in 27.5%, and 12.8% moved to treatment without evidence of progression.

That last figure matters. A meaningful share of men are treated without evidence that the cancer has changed, and the GAP3 authors call for better selection tools to reduce it. Clear information at the start, and an agreed plan, are part of the answer.

Could the biopsy have under-graded the cancer?

Yes, and this is the main reason surveillance begins with a careful second look instead of a simple wait. In a series of 7,643 prostatectomies from 2004 to 2010, 36.3% of cancers graded Gleason 5 to 6 on biopsy were given a higher grade once the whole prostate was examined. Older age, higher PSA, a smaller prostate and more cancer in the biopsy cores made upgrading more likely.

That figure needs context. It comes from men who had already been selected for surgery, in the years before MRI-targeted biopsy was in general use. It should not be read as the risk for a man assessed with MRI today.

MRI narrows the uncertainty. A systematic review found that MRI shows a suspicious lesion in about two thirds of men who otherwise qualify for surveillance, and that among men who went on to prostatectomy, upgrading was found in 43% of those with a positive MRI and 27% of those with a negative one. In the Johns Hopkins cohort, men who had MRI before enrolment were less likely to be reclassified later.

For this reason the EAU guideline gives a strong recommendation to perform MRI before a confirmatory biopsy if it was not done before the first one, and to take targeted cores from any suspicious lesion. Where no MRI preceded the first biopsy, a confirmatory biopsy is done within 6 to 12 months.

When is surgery reasonable for Gleason 6?

When there is evidence that the cancer is, or is becoming, more than low risk, or when a fully informed man decides that surveillance is not for him. The table lists the situations and what the guideline or the studies say about each.

Limits: PSA density, the number of positive cores and MRI findings predict reclassification in groups of men. None of them proves that an individual cancer is aggressive. The BRCA2 finding rests on 11 carriers.

Several of these features are reasons to look again, with MRI and a targeted biopsy, before they are reasons to operate. If treatment is chosen, surgery is not the only route: in ProtecT, radiotherapy gave cancer outcomes similar to prostatectomy. The prostate cancer page describes how the options are weighed and how robotic prostatectomy is carried out.

Age and general health count as well. The guideline asks that life expectancy is assessed before any active treatment is considered in a low-risk patient, because a man unlikely to live long enough to be harmed by the cancer can only be harmed by its treatment.

What do you give up with immediate surgery?

Mainly urinary control and erections, to a degree that differs from man to man, in exchange for a benefit that the trials have not shown in survival for low-risk disease.

The figures in the box come from the patient questionnaires of ProtecT, a randomised trial with response rates above 80% for most measures. They describe operations performed in a trial that recruited from 1999 to 2009, and results vary with age, nerve sparing and the surgeon. PIVOT reported the same direction: urinary incontinence and erectile dysfunction were each greater with surgery than with observation through 10 years. A fuller account is in the article on the side effects of prostate removal.

Surveillance is not free of cost either. In ProtecT, sexual and urinary function in the monitoring group declined gradually with age, and men who later changed to treatment took on its effects at that point.

How hard is it to live with an untreated cancer?

For most men it is easier than they expect, and for a minority it is a real burden that deserves to be taken seriously. The EAU guideline states that anxiety about continuing surveillance occurs in approximately 10% of men.

In ProtecT, where men were randomly assigned, no significant differences were found among the monitoring, surgery and radiotherapy groups in measures of anxiety, depression or general and cancer-related quality of life. These are averages across groups, so they cannot show how any one person will feel.

The guideline recognises anxiety as a valid reason for active treatment and names psychological support as an alternative for men who are otherwise suited to continuing. It also observes that a feeling of lost control feeds uncertainty during surveillance and that regaining a sense of agency can restore confidence. Knowing the schedule in advance, and knowing which result would change the plan, is a practical way to do that.

Which questions should you ask your urologist?

Ask what makes your cancer low risk, and what would change that.

• Is my cancer low risk by the EAU definition, taking my PSA and examination into account?
• Did I have an MRI before the biopsy, and were targeted cores taken from any lesion?
• How many cores contained cancer, and does the report mention cribriform or intraductal growth?
• What is my PSA density?
• Do I need a confirmatory biopsy, and when?
• Which finding would make you advise treatment?
• Is there prostate, breast or ovarian cancer in my family, and should I be tested for BRCA2?
• If I choose treatment, what are my own chances of leakage and erection problems?

For patients from abroad: the first step is a review of your reports (biopsy pathology, PSA history and MRI) by WhatsApp or email, before any travel is planned. For a low-risk Gleason 6 cancer, the advice may well be active surveillance with your own urologist at home, with no operation. If surgery does turn out to be the right choice, the practical steps are described in prostate surgery in Turkey.

This article gives general information and does not replace an assessment of your own scans and results. Treatment is decided individually.